dbSNP rs11079737: WNT3:c.80+7675C>T (chr17-46810843-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030753.5(WNT3):c.80+7675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,018 control chromosomes in the GnomAD database, including 3,824 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3824 hom., cov: 31)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

7 publications found

Variant links:

Genes affected

WNT3 (HGNC:12782): (Wnt family member 3) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]

WNT3 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.80+7675C>T		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4810-238213G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT3	ENST00000225512.6 link	c.80+7675C>T	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5	P56703
WNT3	ENST00000706495.1 link	c.-116+20605C>T	intron_variant	Intron 2 of 5			ENSP00000516418.1	A0A9L9PXJ3
WNT3	ENST00000573788.5 link	n.491+10265C>T	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30386

AN:

151900

Hom.:

3818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.200

AC:

30398

AN:

152018

Hom.:

3824

Cov.:

AF XY:

0.200

AC XY:

14883

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0511

AC:

2120

AN:

41492

American (AMR)

AF:

0.203

AC:

3098

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1118

AN:

3466

East Asian (EAS)

AF:

0.344

AC:

1774

AN:

5150

South Asian (SAS)

AF:

0.269

AC:

1291

AN:

4804

European-Finnish (FIN)

AF:

0.227

AC:

2402

AN:

10562

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17978

AN:

67956

Other (OTH)

AF:

0.202

AC:

427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1152

2305

3457

4610

5762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.246

Hom.:

13926

Bravo

AF:

0.194

Asia WGS

AF:

0.252

AC:

877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.9

(source)

DANN

Benign

0.84

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over